Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma

Neuro Oncol. 2013 Jun;15(6):727-34. doi: 10.1093/neuonc/not012. Epub 2013 Mar 12.

Abstract

Background: Primary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological variables of PCNS-DLBCL.

Methods: Aggregative perivascular tumor cells (APVTs) and reactive perivascular T cell infiltrates (RPVIs) in tumor samples from 62 immunocompetent patients with PCNS-DLBCL were histopathologically and immunohistochemically studied. A mouse brain DLBCL model was established to confirm the special morphological features of PCNS-DLBCL. The therapy, overall response rate (ORR), and overall survival (OS) among patients were followed up.

Results: APVT was present in 54 (87%) of the 62 cases, whereas RPVI was present in 20 (32%). Patients with APVT-positive lesions exhibited significantly worse OS, with intermediate to high International Extranodal Lymphoma Study Group (IELSG) scores, compared with patients with RPVI-positive lesions. Among cases of APVT-positive lymphoma, the semiquantitative score of immunostaining of X-box-binding protein (XBP1) and CD44 demonstrated prognostic significance. Multivariate analysis confirmed independent associations between APVT and XBP1 and between CD44 staining and survival.

Conclusions: The presence of APVT and staining of XBP1 and CD44 are independently associated with survival among patients with PCNS-DLBCL. These features could be routinely assessed in histopathological and immunohistochemical specimens.

Keywords: central nervous system; diffuse large B-cell lymphoma; histopathology; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Central Nervous System Neoplasms / mortality*
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / therapy
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunoenzyme Techniques
  • Immunophenotyping
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Perivascular Epithelioid Cell Neoplasms / mortality*
  • Perivascular Epithelioid Cell Neoplasms / pathology
  • Perivascular Epithelioid Cell Neoplasms / therapy
  • Prognosis
  • Regulatory Factor X Transcription Factors
  • Survival Rate
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Hyaluronan Receptors
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Xbp1 protein, mouse